[phenixbb] covalently linked ligand

Aaron Oakley aarono at uow.edu.au
Wed Apr 15 04:39:38 PDT 2020


I have an enzyme with an inhibitor covalently linked to a cysteine.

The link is from CYS SG to an atom “CAC” in residue “DRG”.

I have a .cif file that contains the geometric parameters of the ligand, AND at the bottom, information to create the link at the end. Hopefully this is self-explanatory...

loop_
_chem_link.id<http://chem_link.id>
_chem_link.comp_id_1
_chem_link.mod_id_1
_chem_link.group_comp_1
_chem_link.comp_id_2
_chem_link.mod_id_2
_chem_link.group_comp_2
_chem_link.name
CYS-DRG  CYS      .        .        DRG      .        . CYS-DRG
#
data_link_CYS-DRG
loop_
_chem_link_bond.link_id
_chem_link_bond.atom_1_comp_id
_chem_link_bond.atom_id_1
_chem_link_bond.atom_2_comp_id
_chem_link_bond.atom_id_2
_chem_link_bond.type
_chem_link_bond.value_dist
_chem_link_bond.value_dist_esd
 CYS-DRG  1 SG      2 CAC       single      1.792    0.010
loop_
_chem_link_angle.link_id
_chem_link_angle.atom_1_comp_id
_chem_link_angle.atom_id_1
_chem_link_angle.atom_2_comp_id
_chem_link_angle.atom_id_2
_chem_link_angle.atom_3_comp_id
_chem_link_angle.atom_id_3
_chem_link_angle.value_angle
_chem_link_angle.value_angle_esd
 CYS-DRG  1  SG     2 CAC     2 CAA  112.576    2.44
 CYS-DRG  1  CB     1  SG     2 CAC  100.595    1.50
 CYS-DRG  1  SG     2 CAC     2 HAC  108.861    1.50
 CYS-DRG  1  SG     2 CAC     2 HAD  108.861    1.50
loop_
_chem_link_tor.link_id
_chem_link_tor.id<http://chem_link_tor.id>
_chem_link_tor.atom_1_comp_id
_chem_link_tor.atom_id_1
_chem_link_tor.atom_2_comp_id
_chem_link_tor.atom_id_2
_chem_link_tor.atom_3_comp_id
_chem_link_tor.atom_id_3
_chem_link_tor.atom_4_comp_id
_chem_link_tor.atom_id_4
_chem_link_tor.value_angle
_chem_link_tor.value_angle_esd
_chem_link_tor.period
 CYS-DRG  sd       1 CB     1 SG     2 CAC    2 CAA     180.00  15.0 3





On 15 Apr 2020, at 8:44 pm, Xavier Brazzolotto <xavier.brazzolotto at chemdef.fr<mailto:xavier.brazzolotto at chemdef.fr>> wrote:

2 solutions that I use

A first one consists in designing your residue linked to your ligand (under ChemDraw / MarvinSketch) then prepare the restraints under eLBOW (from smiles for examples). You will have to modify some atom names into the generated cif file (C, O, CA, N, CB, etc… depending of the modified residue) and above all change the nature of this molecule to L-peptide. Then you can use it in coot as a modified residue and use the modified cif file in Phenix. You can adjust the modification by tuning the occupancy of the atoms corresponding to the ligand and keep the occupancy to 1 for the atoms of the residue. Here you will have a nice covalent bond.

The second solution would be to restrain the distance between the atom of your residue and the atom of the ligand to a covalent bond (C-C distance or whatever it is). Certainly, angles should be restraint too.


Le 15 avr. 2020 à 00:59, Muhammad Bashir Khan <mbk at ualberta.ca<mailto:mbk at ualberta.ca>> a écrit :

Hi All;

I have a protein molecule and a ligand structure. I want to make a covalent bond between the ligand and protein molecule, could somebody explain to me how I can do that using phenix.
 I used the

"  phenix.ligand_linking pdb_file_name"   commond

It creates
apply_link.def
and
data_link.cif

I did refine the structure again giving the above file as well but did not see any covalent bond created between the protein and ligand.

Thanks for your help

Bashir
--
------------------------------------------------------
Muhammad Bashir Khan, Ph.D.
Research Associate
Department of Biochemistry
Medical Science Bldg.
Lab 3-27
University of Alberta
Edmonton AB, T6G 2H7

Phone: 780-492-4577-
e-mail: mbk at ualberta.ca<mailto:cbrooks1 at ualberta.ca>
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Xavier Brazzolotto, PhD
xavier.brazzolotto at chemdef.fr<mailto:xavier.brazzolotto at chemdef.fr>

Département de Toxicologie et Risques Chimiques
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